It is proposed to continue the studies of the effects of three hepatocarcinogens on RNA metabolism in rat liver cells. Previous work has shown that ethionine, dimethylnitrosamine and acetylaminofluorene are potent inhibitors of nuclear RNA synthesis and that this inhibition is a inactivation of the RNA polymerases rather than to effect on the template properties of the nuclear chromatin. Studies to determine the mechanism of this mechanism of this inhibition of the polymerases by each of the carcinogens are proposed. The template properties of the polymerase enzymes from the carcinogen-treated cells will be compared with the normal enzymes. Finally, it is proposed to examine the consequences of such effects on the RNA polymerases on the qualitative pattern of gene expression. The aim of all of these studies is to determine how the interaction of chemical carcinogens with their target cells can lead to the development of altered phenotypes and, thereby, to the development of malignant cells. BIBLIOGRAPHIC REFERENCES: J. Herzog and J.L. Farber. Fibrillar nucleoli do not contain macromolecular precursors of ribosomal RNA. Demonstration by the effects of D-galactosamine. Exp. Cell Res. 93,502, 1975. J. Herzog, A. Serroni, B.A. Briesmeister and J.L. Farber. N-hydroxy-acetylaminofluorene inhibition of rat liver ribonculeic acid polymerase. Cancer Res. 35, 2138, 1975.